• R James White, Karim El-Kersh, Stephan Rosenkranz, Veronica Franco, Carmine Dario Vizza, Roberto Badagliacca, Joanna Pepke-Zaba, Jean Elwing, Rahul G Argula, Shelley Shapiro, Hyoshin Kim, Scott Seaman, Eric Shen, Manisit Das, Meredith Broderick, and Vallerie McLaughlin.
• University of Rochester Medical Center, Rochester, NY 14642, USA.
• Chest. 2024 Nov 30.

BackgroundAn increasing number of patients with pulmonary arterial hypertension (PAH) have cardiovascular comorbidities. However, the effects of comorbidities on responses to PAH treatment are not well understood.Research QuestionDo cardiovascular comorbidities in patients with PAH influence the efficacy and tolerability of inhaled or oral treprostinil?Study Design And MethodsAll patients from phase 3 studies TRIUMPH (N = 235) and FREEDOM-EV (N = 690) were included in this post hoc analysis and were classified as having 0, ≥1, or ≥2 cardiovascular comorbidities of interest based on patients' medical histories. The mean difference in 6-minute walk distance (6MWD) and N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to Week 12 was assessed for TRIUMPH and the risk and incidence of clinical worsening was assessed for patients in FREEDOM-EV. Adverse events (AEs) were summarized for each comorbidity grouping for TRIUMPH and FREEDOM-EV.ResultsIn TRIUMPH, there were 79, 156, and 88 patients with 0, ≥1, and ≥2 comorbidities, respectively. Patients on inhaled treprostinil had improvements in 6MWD, with numerically similar improvements for comorbidity subgroups (0: 26 m, P = 0.020; ≥1: 22 m, P = 0.006; ≥2: 21.6 m, P = 0.043). Significant reductions in NT-proBNP were also seen in all subgroups. In FREEDOM-EV, there were 375, 315, and 166 patients with 0, ≥1, and ≥2 comorbidities, respectively. Regardless of comorbidities, patients on oral treprostinil had a significantly reduced risk of clinical worsening compared with placebo (0: 36% reduction, P = 0.034; ≥1: 41% reduction, P = 0.014; ≥2: 45% reduction, P = 0.026). In TRIUMPH and FREEDOM-EV, AE profiles were typical for this class of medication regardless of the number of comorbidities. A sensitivity analysis using a subset of comorbidities confirmed the findings of our primary analysis.InterpretationThis post hoc analysis suggests that patients with PAH and cardiovascular comorbidities can benefit from combination therapy with inhaled or oral treprostinil.Copyright © 2024. Published by Elsevier Inc.

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